Speakers

In the type 3 (T3) copper proteins of biological systems, the coupled dicopper active site reacts with O2 to form the peroxo intermediate species for O2 transportation and substrate oxygenation. In multicopper oxidases (MCO), the clustering tricopper active site is comprised of a type 2 (T2) and a T3 center, catalyzing reduction of dioxygen to water, accompanied with substrate oxidation. In these systems, the active copper centers with the higher multi-nuclearity perform the more multi-electron reduction of dioxygen. In order to gain insights into their dioxygen activation mechanisms at the active sites in the protein environments, we designed biomimetic copper complex systems having the structural features, (i) distorted coordination geometries and (ii) multi-metal center assembled inside a cavity, respectively.

Using a-isosparteine (aSp) as a highly pre-organized bidentate diamino ligand, we succeeded in synthesizing a carboxylato-bridged butterfly type m–h2: h2-peroxo dicopper(II) complex [CuII2(aSp)2(O2)(Bz)]+ (Bz = benzoate). Bz is one of the well-known inhibitors of tyrosinase, and the coordination mode to the T3 copper site have much relevance to that of substrate, L-tyrosine. Furthermore, these biomimetic dicopper complex systems, using Sp and its stereoisomer, formed low-coordination geometries similar to the proposed intermediate species of particulate methane monooxygenases (pMMO).

For construction of the clustering tricopper complexes, we adopted a bicyclic polyaza cryptand LNH with three bis(2,6-aminomethyl)pyridine spacers as a supporting ligand. We synthesized a tricopper(I) complex [CuI3(LNH)Cl3] as a precursor for formation of the dioxygen adduct complex analogous to that in multicopper oxidases (MCOs). The tricopper(I) complex reacted with dioxygen to form a new oxygenated species. DFT calculation studies on the dioxygen adduct were performed using the crystal structure of a mixed valence tetracopper disulfide complex. In the previous studies on MCOs, Solomon etal. proposed that the Peroxy Intermediate species (PI) generates as an initial 2e–-reduction product of the stepwise dioxygen reduction, producing water molecules. This is the important point of controversy on the reaction mechanism.